Method of using bacteriostatic triphenyltin compounds



United States Patent 3,506,578 METHOD OF USING BACTERIOSTATIC TRIPHENYLTIN COMPOUNDS Kenneth S. Karsten, Westport, and Wilbur S. Taylor, Nor- Walk, 'Conn., assignors to R. T. Vanderbilt Company, Inc., New York N.Y., a corporation of New York No Drawing. Filed June 10, 1966, Ser. No. 556,582 Int. Cl. C11d 9/50 US. Cl. 252-107 12 Claims ABSTRACT OF THE DISCLOSURE Triphenyltin derivatives of the class consisting of triphenyltin hydroxide, triphenyltin 4-acetamidobenzoate, triphenyltin N,N-dimethyldithiocarbamate, triphenylvinyltin, triphenyltin acetate, and triphenyltin oxide are incorporated in skin soaps and shampoos in bacteriostatically effective amounts, generally from about 0.2 to 5% by weight of the total composition. These derivatives maintain their activity in soaps and shampoos and are substantive to the human skin in such formulations This invention relates to cleansing compositions containing skin-substantive 'bacteriostats, and more particularly to soap and shampoo compositions containing bacteriostats consisting of certain trihydrocarbyltin derivatives.

It has become increasingly desirable to obtain detergent compositions that have effective bacteriostatic activity. The term detergent is used herein to denote soap and non-soap surface active agents.

It is fundamental that in order for a bacteriostatic compound to be considered as a desirable additive in a detergent composition, the component must not only maintain its activity in the presence of the detergent but must exhibit the property of skin-substantivity, i.e. the property of remaining on the skin and retaining bacteriostatic activity for a period of time after washing and rinsing the skin.

Many organotin compounds are known as active bacteriostats per se, but, generally speaking, this activity is lost or severely impaired when the organotin compound is included in a detergent composition. Moreover, when most organotin bacteriostatic compounds are incorporated in soap or shampoo and applied in such form to the skin, they are readily rinsed off, leaving little or no effective protection against bacterial growth. It is not surprising, therefore, that organotin compounds have not been known as useful components in bacteriostatic soap or shampoo compositions.

Nonetheless, it has been unexpectedly found that, contrary to the general phenomena, there is a small class of organotin compounds, particularly among the trihydrocarbyltin derivatives, that has both bacteriostatic activity in the presence of detergents and effective skin-substantivity. Until now, both of these important properties were not known to exist in bacteriostatically active organotin compounds, even those few whose activity is not impaired when admixed in a soap composition.

It is, therefore, an object of the present invention to provide a novel detergent composition that is bacteriostatically active and which, when applied to skin, renders it bacteriostatic, even after washing and rinsing thereof.

It is a further object of the present invention to provide a novel soap or shampoo composition containing one or more of certain organotin derivatives that are substantive to skin and that are adapted to give prolonged effect in reducing the number of microorganisms resident on the skin.

, It has been discovered that a limited class of trihydrocarbyltin derivatives consisting of triphenyltin hydroxide, triphenyltin 4-acetamidobenzoate, triphenyltin N,N-dimethyldithiocarbamate, triphenylvinyltin, triphenyltin acetate, triphenyltin oxide has the unusual and unexpected property of being both bacteriostatically active in the presence of detergents and also substantive to skin. The uniqueness of these derivatives is emphasized by the fact that other closely related di-, triand tetra-hydrocarbon substituted tinseven those few which have bacteriostatic activity in the presence of soaphave no significant substantivity to skin.

An experimental study was made which investigated the bacteriostatic activity of many closely related organotin compounds in a soap base and in a shampoo base, and also their resulting skin-substantivity.

In the test for bacteriostatic activity in the presence of the soap base, 1% by weight of the test material (and in some cases 2%) was milled into Ivory soap (of the type made in accordance with US. Patent No. 2,295,594) which was then compressed into tablets. In the case of a liquid shampoo composition, 2% by weight of the organotin compounds *were admixed therewith. Plugs (0.5 inch in diameter and 0.25 inch thick) of each of the test soaps were placed on agar plates each seeded with one of three representative test bacteria, Bacillus subtilis, Staphylococcus aureus, and Salmonella typhosa. The plates were incubated at 37 C. for 24 hours, then examined. The clear zone of inhibition (lack of bacterial growth) around each soap plug was measured and reported as average diameter of zone inhibition (diameter of clear zone less the diameter of the soap plug). The greater the activity of the bacteriostat in the presence of soap, the larger the clear zone denoting lack of bacterial growth.

For the test of substantivity, or retention by the skin of bacteriostat after washing with the test soap or shampoo and rinsing, untanned calf-skin hide buttons were soaked in an 8% solution of the test soap or shampoo containing 1% bacteriostat (a 1% solution thus contains 800 p.p.m. of active bacteriostat and a 2% solution contains 1600 p.p.m. of active bacteriostat), rinsed four times with distilled water, then placed on seeded agar plates, incubated, and the zones of inhibition measured and reported as described above with respect to the activity of soap test. Table I below shows the results of this study for those few substances which exhibited the unusual properties of positive bacteriostatic activity in the presence of soap and shampoo and positive bacteriostatic activity after thorough rinsing.

TABLE I Average diameter of zone of inhibition in mm.

Activity in soap Hide substantivity (soap) 2 Hide substantivity (shampoo) Trih ydrocarb yltin Additive S A '1 S A T S A T Tri-phenyltin hydroxide 6 8 6 3 Tri-phenyltin 4-acetamido-benzoate 2 4 2 1. 5(3) 1(6) 0(2) (6) (3) (8) Tri-phenyltin N ,N-dimethyl dithiocarbamate. 32 36 28 11 8 1O Tri-phenylvinyltin- 5 8 7 2 3 2 Tri phenyltin acetate. 6 4 4 3 4 2 (4) (6) (4) Tri-phenyltin Oxide 6 2 4 1 Key to Table: S =Bacillus subtilis; A=Staphyl0coccus aureus; T=Salmonella typhosa 2 Soap contained 1% organotin compound.

NOTE.Figu1'es in parentheses were obtained from tests using soap or shampoo containing 2% organotin compound.

The results of Table I were surprising in view of the fact that organotin compounds by and large show little or no bacteriostatic activity in the presence of soap. Indeed, testing of many organotin compounds closely analogous to those of Table I showed that they either lacked bacteriostatic activity in the presence of soap or lacked skin-substantivity, or both. For example, the following highly bacteriostatically active organotin compounds showed little or no eflicacy against one or more of the three strains of bacteria referred to above in Table I when incorporated in a soap composition and tested in the same manner as those reported in Table I: tri-n-propyltin methacrylate, tri-n-propyltin fluoride, tri-n-propyltin benzoate, tribenzyltin acetate, tribenzyltin chloride, triphenyltin chloride, triphenyltin fluoride, tributyltin oxide, tributyltin acetate, tributyltin linoleate, tetraallyltin, tetrabutyltin, tetraphenyltin, tetraoctyltin, dibutyltin maleate, dibutyltin bis(methane thiosulfonate), dibutyltin N,N-diamyldithiocarbamate, dibutyltin N,N-dilauryldithiocarbamate, dibutyltin diethanoldithiocarbamate, dibutyltin piperazinodithiocarbamate, diethyltindichloride, dioctyltin oxide and dioctyltin dichloride.

Moreover, even when some of these compounds were found to be effective against some bacteria, there was no assurance that the compound would be substantive to skin or would show a persistence of even limited bacteriostatic activity. In this respect the following organotin compounds having some activity in the presence of soap were found to lack substantivity, i.e., their limited eflicacy did not persist under the conditions required by the usages of the present invention: tri-n-propyltin fluoride, tri-npropyltin benzoate, dibutyltin N,N-diethanoldithiocarbamate, tributyltin N,N-diamyldithiocarbamate, tributyltin sulfosalicylate and tributyltin linoleate.

Therefore, it has been discovered, unexpectedly, that among the organotin compounds only certain triphenyltin and tripropyltin derivatives exhibit both significant bacteriostatic activity and substantivity to skin.

Since the specific activities of the trihydrocarbyltin compounds differ from each other, the particular level of activity desired is a matter of choice depending on the nature of the application and the particular compound used. In general, however, concentrations in the range of 0.2 to 5% by weight are adequate to achieve a desired level of activity for most applications.

The soap used in the comparative tests described was a proprietary non-germicidal soap sold under the trademark Ivory and whose composition is basically a mixture of alkali-metal salts of fatty acids as listed below:

Concentration Acids: percent Oleic and linoleic acid 46 Stearic acid 14 Palmitic acid 30 Lower fatty acid (myristic, lauric, etc.)

However, the invention is not limited to soaps of the above fatty acids and, in general, the soaps of the sodium, potassium, amine, ammonium or alkanol-ammonium salts of the higher fatty acids (C -C are satisfactory.

The specific shampoo formulation used in the tests reported in Table I was a synthetic anionic surfactant formulation having the composition (by weight):

Percent Sodium lauryl sulfate 23 Sodium sulfate 1 Sodium stearate 9 Water 67 However, a much broader range of surfactants can be used as the detergent base for shampoo or other products incorporating the composition of the invention. Examples are water soluble salts such as alkyl glyceryl ether sulfonates, alkyl sulfates, alkyl monoglyceride sulfates or sulfonates, alkyl polyethoxy ether sulfates, acyl sarcosinates, acyl esters of isethionates, acyl N-methyl taurides, alkyl benzene sulfonates, and alkyl phenol polyethoxy sulfonates, or certain quaternary ammonium salts such as dilauryldimethyl ammonium chloride, diisobutyl phenoxy ethoxy ethyl dimethylbenzyl ammonium chloride, cetyl trimethyl ammonium bromide, N-cetyl pyridinium bromide and benzethonium chloride and mixtures of such surfactants.

It is seen that the invention concerns detergent compositions incorporating a small percentage of one or more bacteriostatically active components selected from the class of trihydrocarbon compounds consisting of Odits-Sn-Y wherein Y is a radical selected from the group consisting of acetate, hydroxyl, vinyl, acetamidobenzoate, N,N-dimethyl dithiocarbamate and oxygen.

These compositions, when applied to skin or scalp, leave a substantive bacteriostatically active component which is effective in controlling the growth of bacteria. As a result, infections are less likely to occur and spread, and body odors are more likely to be checked. The bacteriostatic effect is relatively long lasting as compared to that of soaps and shampoos containing no bacteriostatic component or even that of soaps or shampoos containing nonskin-substantive bacteriostatically active components.

Among the limited group of compounds found operative for an effective germicidal soap, there are, of course, specific differences. It is indicated in Table I that triphenyltin N,N-dimethyldithiocarbamate has, for a given concentration, a broader range of inhibition of bacterial growth than do the other trihydrocarbyltin derivatives. Consequently, a given level of germicidal activity is achieved with a lesser quantity of the N,N-dimethyldithiocarbamate derivative than is the case with the remaining members of the class.

Considerations other than higher activity for a given concentration may, however, dictate the choice of one of the trihydrocarbyltin derivatives for a certain contemplated end use. The hydroxide derivative of triphenyltin, for example, is, at present, less costly to manufacture than the N,N-dimethyldithiocarbamate; further, it tends to give advantageous color retention and odor characteristics. Consequently, for compositions where these characteristics are paramount, the hydroxyl derivative is currently preferred.

Normal soap additives, such as dyes, perfumes, inert fillers, emollients and the like can be used without significant impairment of the qualities of the soap or shampoo compositions. Further, the detergent portion of the combination can, of course, be usefully employed either in liquid, semi-solid, granular or bar form.

What is claimed is:

1. The method of protecting the human skin and scalp against infectious bacteria comprising applying to said skin or scalp a cleansing composition consisting essentially of a mixture of a detergent selected from the group consisting of alkali metal fatty acid soaps and anionic and cationic synthetic detergents and a bacteriostatically effective amount of a bacteriostatic compound selected from the class consisting of:

oiH5snY wherein Y is a radical selected from the group consisting of acetate, hydroxide, vinyl, acetamido benzoate, N,N-

dimethyldithiocarbamate and oxygen, and thereafter rinsing said skin or scalp.

2. The method according to claim 1 wherein the concentration of the bacteriostatic compound in the cleansing composition is from 0.2 to 5% by weight of the total composition.

3. The method according to claim 1 wherein the detergent is a soap composed substantially of alkali metal salts of acids selected from the class consisting of oleic, linoleic, stearic, myristic, lauric and palmitic.

4. The method according to claim 1 wherein the detergent is a soap selected substantially from the alkali, ammonium or alkanol ammonium salts of fatty acids having from 10 to 20 carbon atoms.

5. The method according to claim 1 wherein the bacteriostatic compound is triphenyltin hydroxide.

6. The method according to claim 1 wherein the bacteriostatic compound is triphenyltin 4-acetamidobenzoate.

7. The method according to claim 1 wherein the bac teriostatic compound is triphenyltin N,N-dimethyldithiocarbamate.

8. The method according to claim 1 wherein the bacteriostatic compound is triphenylvinyltin.

9. The method according to claim 1 wherein the bacteriostatic compound is triphenyltin oxide.

References Cited UNITED STATES PATENTS 3,031,483 4/1962 Koopmans 260-429] 3,159,531 12/1964 Bruckner et a1 16713 3,222,158 12/1965 Sowa 252-106 3,256,143 5/ 1966 Zedler 252-106 MAYER WEINBLATI, Primary Examiner P. E. WILLIS, Assistant Examiner US. Cl. X.R. 

